Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress

Area of Science:

• Lymphatic biology
• Cellular transport mechanisms
• Immunology

Background:

• Lymphatic endothelial cells (LECs) are vital for interstitial fluid balance and immune surveillance.
• Transendothelial transport is traditionally viewed as paracellular, driven by pressure and concentration gradients.
• Emerging evidence suggests LECs actively regulate solute transport via transcellular pathways.

Purpose of the Study:

• To compare the significance of transcellular (vesicular) versus paracellular transport pathways in LECs.
• To investigate how mechanical stress, specifically fluid flow, influences these transport routes.

Main Methods:

• Quantified intracellular solute uptake versus transendothelial transport in vitro.
• Utilized fluorescently labeled albumin to track solute transport in vivo and in vitro.
• Applied transmural flow conditioning to LECs and assessed the impact of dynamin inhibition on vesicle formation.

Main Results:

• Transcellular transport, involving caveolae- and clathrin-coated vesicles, significantly contributes to lymphatic solute transport.
• In vivo, LECs exhibited albumin uptake comparable to dermal dendritic cells.
• In vitro, transmural flow (1 µm/s) increased LEC solute uptake and transport, which was reversible by inhibiting dynamin-dependent vesicle formation.

Conclusions:

• Intracellular transport is crucial for steady-state lymph formation.
• LECs employ transcellular mechanisms alongside paracellular routes to regulate interstitial solute transport.
• Biomechanical cues, like fluid flow, modulate LEC transcellular transport activity.